CD33 rs3865444 as a risk factor for Parkinson's disease.

BACKGROUND: Alzheimer's (AD) and Parkinson's diseases (PD) share a few elements of their clinical, pathological and genetic backgrounds. The CD33 rs3865444 has emerged as a strong genetic locus associated with AD through genome-wide association study (GWAS). However, little is known for its role in PD. OBJECTIVE: To assess the role of CD33 rs3865444 on PD risk. METHODS: We genotyped 358 patients with PD and 358 healthy controls for theCD33 rs3865444. Odds ratios (ORs) with the respective 95% confidence intervals (CIs)], were calculated with the SNPStats software, assuming five genetic models (co-dominant, dominant, recessive, over-dominant and log-additive), with the G allele as the reference allele. RESULTS: The CD33 rs3865444 was associated with decreased PD risk in the dominant [GG vs GT + TT; OR (95% CI) = 0.61 (0.45-0.82), p = 0.001], the over-dominant [GG + TT vs GT; OR (95% CI) = 0.65 (0.48-0.89), p = 0.0061], log-additive [OR (95% CI) = 0.67 (0.52-0.86), p = 0.0014], and co-dominant [with overall p = 0.0043, and OR (95% CI) = 0.62 (0.45-0.84) for the TG genotype compared to the GG], modes of inheritance. CONCLUSIONS: The CD33 rs3865444 is associated with decreased PD risk, and larger studies investigating the role of CD33 rs3865444 on PD are needed.

SLC2A3 rs12842 polymorphism and risk for Alzheimer's disease.

BACKGROUND: Many studies support the hypothesis that brain glucose dysregulation contributes to neurodegeneration and disease progression. The SLC2A3 gene encodes the Neuronal Glucose Transporter 3 (GLUT3), a critical molecule for glucose transport into the neuron. The GLUT3 rs12842 polymorphism has been associated with an increased risk for attention-deficit/hyperactivity disorder (ADHD). Epidemiological and genetic studies have reported a link between antecedent ADHD and Alzheimer's disease (AD), as both share a dysregulation of brain glucose. AIM: This study aimed to explore the possible correlation of the SLC2A3 rs12842 polymorphism with susceptibility towards AD. METHODS: We genotyped 327 patients with AD and 327 controls for the GLUT3 rs12842. Results: Rs12842 was associated with a decreased risk of developing AD in the co-dominant [Odds Ratio (OR) (95% confidence interval (CI) = 0.67 (0.45-0.99)), p = 0.039], dominant [OR (95% CI) = 0.64 (0.44-0.93), p = 0.019] and log-additive modes [OR (95% CI) = 0.65 (0.46-0.91), p = 0.012]. CONCLUSIONS: Our results suggest a significant, inverse association between SLC2A3 rs12842 and the risk of AD.

Does the CD33 rs3865444 Polymorphism Confer Susceptibility to Alzheimer's Disease?

Alzheimer's disease (AD) is a complex genetic disorder. To date, published data have reported conflicting results on the role of CD33 rs3865444 polymorphism in AD. The present study aimed at evaluating the effect of rs3865444 on AD in a large cohort of Greek native patients with AD. We also conducted a meta-analysis by pooling information from different studies on the same topic. Patients with AD (n = 327) and healthy controls (n = 327) were analyzed and genotyped for rs3865444. Single locus analyses were run to explore possible associations between CD33 rs3865444 polymorphism and AD. Our analysis yielded no significant interaction between AD and the CD33 rs3865444 polymorphism. The lack of interaction between the two variables persisted even after a pooled meta-analysis of 8 studies (with 13 datasets), with 4015 AD cases and 7981 controls. The overall results do not support the hypothesis that CD33 rs3865444 polymorphism increases the risk of AD. The results also suggest that the identification of functional variants in CD33 that are indisputably correlated with AD may be an important factor to investigate in future genetic screening studies.

Does SCFD1 rs10139154 Polymorphism Decrease Alzheimer's Disease Risk?

Α number of genetic variants have been associated with Alzheimer's disease (AD) susceptibility. Sec1 family domain-containing protein 1 (SCFD1) gene polymorphism rs10139154 has recently been implicated in the risk of developing amyotrophic lateral sclerosis (ALS). Similarities in the pathogenetic cascade of both diseases have also been described. The present study was designed to evaluate the possible contribution of SCFD1 rs10139154 to AD. A total of 327 patients with AD and an equal number of healthy controls were included in the study and genotyped for rs10139154. With logistic regression analyses, rs10139154 was examined for the association with the risk of developing AD. In the recessive mode, SCFD1 rs10139154 was associated with a decreased risk of developing AD (odds ratio (OR) (95% confidence interval (CI)) = 0.63 (0.40-0.97), p = 0.036). The current study provides preliminary evidence of the involvement of SCFD1 rs10139154 in the risk of developing AD.

Vitamin B12, folate, and homocysteine levels and multiple sclerosis: A meta-analysis.

BACKGROUND: Multiple sclerosis (MS) is a demyelinating and disabling inflammatory disease of the central nervous system. Several factors contribute to MS pathogenesis including genetic-environmental interactions. Case-control studies suggest that there might be associations between MS and homocysteine (Hcy), vitamin B12, and folate blood levels. AIM: To meta-analyze all available data describing associations between MS and serum or plasma Hcy, vitamin B12, and folate levels. METHODS: The PubMed, MEDLINE, and EMBASE databases were searched for eligible case-control studies published until June 2017. After data extraction, separate analyses using mainly random-effects models were conducted to test for associations between MS and vitamin B12, Hcy, or folate blood levels. RESULTS: Twelve, 12, and 9 studies met the inclusion criteria for meta-analysis of MS and Hcy, vitamin B12, and folate levels, respectively. The standardized mean difference (SMD) between MS patients and controls was statistically significant for Hcy (SMD: 0.70, 95% CI: 0.06, 1.34). Stratification according to clinical pattern did not reveal significant differences between relapsing-remitting MS patients and controls (SMD: 0.30, 95% CI: -0.93, 1.54) or between secondary progressive MS patients and controls (SMD: 0.12, 95% CI: -1.65, 1.90). There were no significant differences in SMD between MS patients and healthy individuals for vitamin B12 (SMD: -0.09, 95% CI: -0.29, 0.10) or folate (SMD: -0.06, 95% CI: -0.17, 0.05). CONCLUSION: MS patients tend to have elevated Hcy blood levels compared to healthy controls. Hcy may contribute to the pathogenesis of the disease.

Deciphering the role of DNA methylation in multiple sclerosis: emerging issues.

Multiple sclerosis (MS) is an autoimmune inflammatory and neurodegenerative disease of the central nervous system that involves several not yet fully elucidated pathophysiologic mechanisms. There is increasing evidence that epigenetic modifications at level of DNA bases, histones, and micro-RNAs may confer risk for MS. DNA methylation seems to have a prominent role in the epigenetics of MS, as aberrant methylation in the promoter regions across genome may underlie several processes involved in the initiation and development of MS. In the present review, we discuss current understanding regarding the role of DNA methylation in MS, possible therapeutic implications and future emerging issues.

HIV infection and depression.

Major depression is highly prevalent among HIV-positive patients (HIVpp). The prevalence of depression ranges between 18% and 81%, depending on the population studied and the methodology of the study. The etiology of depression in HIVpp is likely determined by: (i) biological factors (alterations in the white matter structure, hypothalamic-pituitary-thyroid dysfunction, Tat-protein-induced depressive behavior); (ii) psychosocial factors (HIV stigma, occupational disability, body image changes, isolation and debilitation); (iii) history or comorbidity of psychiatric illness; and (iv) the perinatal period in HIVpp women. Symptomatology of depression differs between HIVpp and HIV-negative patients (HIVnp). Depression may also alter the function of lymphocytes in HIVpp and decrease natural killer cell activity, contributing to the increased mortality in these patients. Selective serotonin re-uptake inhibitors are considered the first-line treatment. Treatment of depression can improve quality of life and lead to a better prognosis of HIV infection.